Ristocetin-induced platelet aggregation was studied using the platelet rich plasma (PRP) and gel filtered platelets (GFP) of normal people and patients with von Willebrand's disease. Gel filtration removed over 99.5% of the plasma proteins from the platelets. Ristocetin aggregation was not uniformly present in the PRP of 7 normals. In some cases, the absence of ristocetin aggregation could be traced to aspirin ingestion. The addition of aspirin to the PRP of normal people abolished ristocetin-induced aggregation. Following gel filtration, ristocetin-induced aggregation was present for all normal subjects' platelets, even if aspirin was added to the GFP. The PRP and GFP of 3 patients with von Willebrand's disease did not aggregate in the presence of ristocetin. The addition of normal plasma to von Willebrand's GFP corrected the response; however, the addition of normal plasma to the PRP of patients with von Willebrand's disease did not correct the abnormal ristocetin response. High molecular weight fractions obtained by gel filtration of factor VIII concentrates also corrected the ristocetin response of the von Willebrand GFP. Two peaks of factor VIII activity eluted during gel filtration of factor VIII concentrates; however, only the high molecular weight (void volume) fractions corrected the abnormal ristocetin response. There was little correlation between the amount of factor VIII procoagulant activity in a fraction and its ability to correct the abnormal ristocetin response of von Willebrand's GFP. These studies suggest that the ristocetin-induced aggregation is mediated through a high molecular weight plasma component which co-chromatographs with the normal platelet during gel filtration. In von Willebrand's disease this plasma component is altered such that it inhibits the correction of the ristocetin-induced aggregation by either plasma or plasma fractions. The plasma component appears to be physically modified in some way such that it can be removed by gel filtration, since the von Willebrand GFP is corrected by plasma and plasma fractions.
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